Portal de Periódicos da CAPES

A Practical Guideline for Management of Hypertension in Patients With Diabetes

1996; Elsevier BV; Volume: 71; Issue: 1 Linguagem: Inglês

10.4065/71.1.53

1942-5546

Vahab Fatourechi, Frank P. Kennedy, Robert A. Rizza, Michael J. Hogan,

Pharmacology and Obesity Treatment

Hypertension is common in patients with non-insulin-dependent diabetes mellitus and is also an early sign of diabetic nephropathy in those with insulin-dependent diabetes. Hypertension contributes to the progression of both macrovascular disease and nephropathy in patients with diabetes. Certain antihypertensive agents can adversely affect carbohydrate and lipid metabolism. Angiotensin-converting enzyme inhibitors and calcium channel blockers may slow the progression of renal complications in patients with diabetes. The pharmacologic approaches to treatment of hypertension in patients with diabetes potentially differ from those in nondiabetic persons. On the basis of a review of the recent literature related to antihypertensive therapy for patients with diabetes, we describe an empiric approach to treatment of hypertension in such patients. The proposed approach must be modified as new data from randomized clinical trials become available. Hypertension is common in patients with non-insulin-dependent diabetes mellitus and is also an early sign of diabetic nephropathy in those with insulin-dependent diabetes. Hypertension contributes to the progression of both macrovascular disease and nephropathy in patients with diabetes. Certain antihypertensive agents can adversely affect carbohydrate and lipid metabolism. Angiotensin-converting enzyme inhibitors and calcium channel blockers may slow the progression of renal complications in patients with diabetes. The pharmacologic approaches to treatment of hypertension in patients with diabetes potentially differ from those in nondiabetic persons. On the basis of a review of the recent literature related to antihypertensive therapy for patients with diabetes, we describe an empiric approach to treatment of hypertension in such patients. The proposed approach must be modified as new data from randomized clinical trials become available. Hypertension is common in patients with diabetes mellitus1Fuller JH Hypertension and diabetes: epidemiologic aspects as a guide to management.J Cardiovasc Pharmacol. 1993; 21: S63-S66Crossref PubMed Scopus (7) Google Scholar and contributes to the development of chronic diabetic complications.2The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V).Arch Intern Med. 1993; 153: 154-183Crossref PubMed Scopus (2782) Google Scholar, 3Ritz E Hypertension in diabetic nephropathy: prevention and treatment.Am Heart J. 1993; 125: 1514-1519Abstract Full Text PDF PubMed Scopus (15) Google Scholar, 4Nosadini R Fioretto P Trevisan R Crepaldi G Insulin-dependent diabetes mellitus and hypertension.Diabetes Care. 1991; 14: 210-219Crossref PubMed Scopus (28) Google Scholar, 5Weidmann P Ferrari P Central role of sodium in hypertension in diabetic subjects.Diabetes Care. 1991; 14: 220-232Crossref PubMed Scopus (108) Google Scholar Antihypertensive medications traditionally used as initial therapy for nondiabetic persons may not be the drugs of choice for the treatment of hypertension in patients with diabetes mellitus. For example, thiazide diuretics may inhibit insulin secretion and increase blood lipid concentrations.2The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V).Arch Intern Med. 1993; 153: 154-183Crossref PubMed Scopus (2782) Google Scholar, 6Shapiro AP Benedek TG Small JL Effect of thiazides on carbohydrate metabolism in patients with hypertension.N Engl J Med. 1961; 265: 1028-1033Crossref Google Scholar β-Adrenergic blocking agents may increase lipids, inhibit insulin secretion, impair glucose counterregulation, and block the adrenergic symptoms of hypoglycemia, making recognition of an episode of hypoglycemia difficult.7Newman RJ Comparison of propranolol, metoprolol, and acebutolol on insulin-induced hypoglycaemia.BMJ. 1976; 2: 447-449Crossref PubMed Scopus (59) Google Scholar, 8Rohlfing JJ Brunzell JD The effects of diuretics and adrenergic-blocking agents on plasma lipids.West J Med. 1986; 145: 210-218PubMed Google Scholar Compelling evidence now shows that angiotensin-converting enzyme (ACE) inhibitors reduce proteinuria and slow the progression of nephropathy in patients with diabetes.9Williams GH Converting-enzyme inhibitors in the treatment of hypertension.N Engl J Med. 1988; 319: 1517-1525Crossref PubMed Google Scholar, 10Overlack A Adamczak M Bachmann W Bonner G Bretzel RG Derichs R et al.ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases.Am J Med. 1994; 97: 126-134Abstract Full Text PDF PubMed Scopus (44) Google Scholar, 11Bain R Rohde R Hunsicker LG McGill J Kobrin S Lewis EJ et al.A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics.J Am Soc Nephrol. 1992; 3: S97-S103PubMed Google Scholar, 12Arauz-Pacheco C Raskin P Management of hypertension in diabetes.Endocrinol Metab Clin North Am. 1992 Jun; 21: 371-394PubMed Google Scholar, 13Lewis EJ Hunsicker LG Bain RP Rohde RD The effect of angiotensin-converting-enzyme inhibition in diabetic nephropathy.N Engl J Med. 1993; 329: 1456-1462Crossref PubMed Scopus (5024) Google Scholar Therefore, alternative drugs such as ACE inhibitors or calcium channel blocking agents13Lewis EJ Hunsicker LG Bain RP Rohde RD The effect of angiotensin-converting-enzyme inhibition in diabetic nephropathy.N Engl J Med. 1993; 329: 1456-1462Crossref PubMed Scopus (5024) Google Scholar, 14Ferrier C Ferrari P Weidmann P Keller U Beretta-Piccoli C Riesen WF Antihypertensive therapy with Ca2+: antagonist verapamil and/or ACE inhibitor enalapril in NIDDM patients.Diabetes Care. 1991; 14: 911-914Crossref PubMed Scopus (38) Google Scholar, 15Caldwell BV Treating hypertension in the diabetic patient: therapeutic goals and the role of calcium channel blockers.Clin Ther. 1993; 15: 618-636PubMed Google Scholar, 16ter Wee PM De Micheli AG Epstein M Effects of calcium antagonists on renal hemodynamics and progression of nondiabetic chronic renal disease.Arch Intern Med. 1994; 154: 1185-1202Crossref PubMed Google Scholar may be more appropriate for the treatment of hypertension in patients with diabetes. The American Diabetes Association,17American Diabetes Association Standards of medical care for patients with diabetes mellitus.Diabetes Care. 1995; 18: 9-15Google Scholar Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC),2The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V).Arch Intern Med. 1993; 153: 154-183Crossref PubMed Scopus (2782) Google Scholar and Canadian Hypertension Society18Dawson KG McKenzie JK Ross SA Chiasson J-L Hamet P Report of the Canadian Hypertension Society Consensus Conference. 5. Hypertension and diabetes.Can Med Assoc J. 1993; 149: 821-826Google Scholar have recently published their recommendations. Herein we discuss a suggested, albeit still primarily empiric, approach to the treatment of hypertension in patients with diabetes mellitus. Even with normal blood pressure levels, microalbuminuria is a risk factor for atherosclerosis and renal disease in patients with type I (insulin-dependent) diabetes. Several trials have shown that a decrease in microalbuminuria slows progression of renal disease.11Bain R Rohde R Hunsicker LG McGill J Kobrin S Lewis EJ et al.A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics.J Am Soc Nephrol. 1992; 3: S97-S103PubMed Google Scholar, 13Lewis EJ Hunsicker LG Bain RP Rohde RD The effect of angiotensin-converting-enzyme inhibition in diabetic nephropathy.N Engl J Med. 1993; 329: 1456-1462Crossref PubMed Scopus (5024) Google Scholar Therefore, even a borderline increase in blood pressure (for example, 140/90 mm Hg) should be treated.17American Diabetes Association Standards of medical care for patients with diabetes mellitus.Diabetes Care. 1995; 18: 9-15Google Scholar Both the American Diabetes Association and the JNC recommend a goal of 130/85 mm Hg or lower in adult patients with diabetes. The diagnosis of hypertension should be based on obtaining seated blood pressure readings on several occasions.17American Diabetes Association Standards of medical care for patients with diabetes mellitus.Diabetes Care. 1995; 18: 9-15Google Scholar On each occasion, however, the patient should be allowed to rest quietly before the measurement is obtained. Alternatively, ambulatory and home blood pressure monitoring can aid in diagnosis;19Bottini PB Prisant LM Carr AA Automated blood pressure monitoring: should it be used routinely in managing hypertension?.Postgrad Med. 1994 May 1; 95 (93-94; 96; 101-102; 106-108): 89-90PubMed Google Scholar however, large-scale epidemiologic or interventional studies have yet to establish these two techniques as diagnostic. Most people with diabetes and hypertension have “essential” (no identifiable underlying cause) hypertension. Contributing factors include daily consumption of more than 1 oz of alcohol, high intake of salt, lack of exercise, and family history of hypertension. Risk factors for the development of vascular disease include smoking and hyperlipidemia. Resistance to adequate doses of medication, sudden onset of hypertension, or unexplained deterioration of previously controlled blood pressure should suggest the existence of a secondary cause of hypertension. Other clues for the presence of secondary types of hypertension in untreated persons include unprovoked hypokalemia (hyperaldosteronism), a postural decrease in systolic blood pressure of more than 30 mm Hg with and without symptoms of sympathetic overactivity (a pheochromocytoma), physical signs of glucocorticoid excess (Cushing's syndrome), and detection of an abdominal bruit (renovascular disease). The blood pressure level should be measured during the first visit while the patient is supine, sitting, and standing. A substantial decrease in systolic blood pressure is unusual in patients with essential hypertension. The fundi should be examined for evidence of vascular changes. The carotid, abdominal, and femoral regions should be auscultated for bruits. Detection of a bruit suggests peripheral vascular disease. The blood pressure level should be measured in both arms to ensure comparability and to exclude a proximal coarctation of the aorta. If laboratory tests have not been done within the previous 3 months, blood specimens should be obtained to determine serum sodium and potassium, cholesterol, triglyceride, high-density lipoprotein cholesterol, calcium, phosphate, uric acid, and creatinine levels and for liver function tests. A urine specimen should be analyzed for proteinuria (including microalbuminuria) and, in some cases, sodium and potassium excretion. Baseline urinalysis, a chest roentgenogram, and an electrocardiogram are needed in most patients. Evaluation of secondary causes of hypertension, if suspected, may necessitate further investigation and appropriate consultations. Nonpharmacologic measures and lifestyle modification, as outlined by the JNC, should be the initial management. Such a regimen involves (1) cessation of cigarette smoking; (2) reduction of weight, if indicated; (3) modification of alcohol consumption; (4) performance of regular aerobic activity, 30 to 40 minutes three to four times per week; (5) reduction of dietary sodium; (6) assurance that intake of calcium (about 800 to 1,000 mg/day) and potassium is adequate; and (7) consumption of a low-fat, low-cholesterol diet to prevent or treat dyslipidemia. Having patients measure their own blood pressure levels at regular intervals and record the results in their diabetes record books may be helpful. If the blood pressure level remains abnormal after 3 to 4 months of lifestyle modification and if the initial increased blood pressure determinations are moderate to severe or if microalbuminuria is a concern (Fig. 1, Fig. 2), drug therapy should be considered.Fig. 2Algorithm for treatment of hypertension in patients with type II diabetes (NIDDM). K = potassium. For explanation of other abbreviations, see Figure 1. * = If side effects develop, go to next stage. If side effects develop with higher dose, decrease dose and add next stage. ** = Use low-dose hydrochlorothiazide. Use furosemide when serum creatinine level is more than 2 mg/dL and if nephrotic syndrome is present. If hyperlipidemia is a problem, indapamide could be used. *** = Do not use in patients with orthostatic hypotension or severe autonomy neuropathy.View Large Image Figure ViewerDownload (PPT) According to the JNC, no antihypertensive agent is specifically contraindicated in patients with uncomplicated diabetes. We agree that low-dose thiazides and β-blockers may have minimal adverse metabolic effects; however, the preponderance of available information suggests added beneficial effects with ACE inhibitors and possibly calcium channel blockers in patients with diabetes and hypertension.2The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V).Arch Intern Med. 1993; 153: 154-183Crossref PubMed Scopus (2782) Google Scholar, 3Ritz E Hypertension in diabetic nephropathy: prevention and treatment.Am Heart J. 1993; 125: 1514-1519Abstract Full Text PDF PubMed Scopus (15) Google Scholar, 4Nosadini R Fioretto P Trevisan R Crepaldi G Insulin-dependent diabetes mellitus and hypertension.Diabetes Care. 1991; 14: 210-219Crossref PubMed Scopus (28) Google Scholar, 5Weidmann P Ferrari P Central role of sodium in hypertension in diabetic subjects.Diabetes Care. 1991; 14: 220-232Crossref PubMed Scopus (108) Google Scholar, 6Shapiro AP Benedek TG Small JL Effect of thiazides on carbohydrate metabolism in patients with hypertension.N Engl J Med. 1961; 265: 1028-1033Crossref Google Scholar, 7Newman RJ Comparison of propranolol, metoprolol, and acebutolol on insulin-induced hypoglycaemia.BMJ. 1976; 2: 447-449Crossref PubMed Scopus (59) Google Scholar, 8Rohlfing JJ Brunzell JD The effects of diuretics and adrenergic-blocking agents on plasma lipids.West J Med. 1986; 145: 210-218PubMed Google Scholar, 9Williams GH Converting-enzyme inhibitors in the treatment of hypertension.N Engl J Med. 1988; 319: 1517-1525Crossref PubMed Google Scholar, 10Overlack A Adamczak M Bachmann W Bonner G Bretzel RG Derichs R et al.ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases.Am J Med. 1994; 97: 126-134Abstract Full Text PDF PubMed Scopus (44) Google Scholar, 11Bain R Rohde R Hunsicker LG McGill J Kobrin S Lewis EJ et al.A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics.J Am Soc Nephrol. 1992; 3: S97-S103PubMed Google Scholar, 12Arauz-Pacheco C Raskin P Management of hypertension in diabetes.Endocrinol Metab Clin North Am. 1992 Jun; 21: 371-394PubMed Google Scholar, 13Lewis EJ Hunsicker LG Bain RP Rohde RD The effect of angiotensin-converting-enzyme inhibition in diabetic nephropathy.N Engl J Med. 1993; 329: 1456-1462Crossref PubMed Scopus (5024) Google Scholar, 14Ferrier C Ferrari P Weidmann P Keller U Beretta-Piccoli C Riesen WF Antihypertensive therapy with Ca2+: antagonist verapamil and/or ACE inhibitor enalapril in NIDDM patients.Diabetes Care. 1991; 14: 911-914Crossref PubMed Scopus (38) Google Scholar, 15Caldwell BV Treating hypertension in the diabetic patient: therapeutic goals and the role of calcium channel blockers.Clin Ther. 1993; 15: 618-636PubMed Google Scholar, 16ter Wee PM De Micheli AG Epstein M Effects of calcium antagonists on renal hemodynamics and progression of nondiabetic chronic renal disease.Arch Intern Med. 1994; 154: 1185-1202Crossref PubMed Google Scholar The renoprotective effects of thiazides and β-blockers in patients with diabetes are less clear; thus, caution is needed in their use in such patients. The use of thiazides and β-blockers may be influenced by the presence of concomitant diseases such as chronic obstructive pulmonary disease, angina, peripheral vascular disease, gout, and hyperlipidemia. Cost and side effects of medications also should be considered. ACE inhibitors have been shown to have renoprotective effects in patients with insulin-dependent diabetes mellitus if microalbuminuria is present. These agents should be used cautiously, if at all, in patients with non-insulin-dependent diabetes mellitus who have evidence of renal artery stenosis or advanced renal failure.11Bain R Rohde R Hunsicker LG McGill J Kobrin S Lewis EJ et al.A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics.J Am Soc Nephrol. 1992; 3: S97-S103PubMed Google Scholar, 12Arauz-Pacheco C Raskin P Management of hypertension in diabetes.Endocrinol Metab Clin North Am. 1992 Jun; 21: 371-394PubMed Google Scholar, 13Lewis EJ Hunsicker LG Bain RP Rohde RD The effect of angiotensin-converting-enzyme inhibition in diabetic nephropathy.N Engl J Med. 1993; 329: 1456-1462Crossref PubMed Scopus (5024) Google Scholar, 17American Diabetes Association Standards of medical care for patients with diabetes mellitus.Diabetes Care. 1995; 18: 9-15Google Scholar, 18Dawson KG McKenzie JK Ross SA Chiasson J-L Hamet P Report of the Canadian Hypertension Society Consensus Conference. 5. Hypertension and diabetes.Can Med Assoc J. 1993; 149: 821-826Google Scholar Various ACE inhibitors are available (Table 1). Treatment should be initiated with low doses, and then doses should be gradually increased. Patients should be asked about the presence of cough and loss of taste, rash, or angioedema.1Fuller JH Hypertension and diabetes: epidemiologic aspects as a guide to management.J Cardiovasc Pharmacol. 1993; 21: S63-S66Crossref PubMed Scopus (7) Google Scholar, 20Sunman W Sever PS Non-angiotensin effects of angiotensin-converting enzyme inhibitors [edtiorial].Clin Sci. 1993; 85: 661-670PubMed Google Scholar The cough that occurs with ACE inhibitor therapy may be mild, and thus discontinuation of use of the medication may be unnecessary. The angiotensin II receptor antagonist losartan potassium seems to be as effective as an ACE inhibitor in lowering blood pressure and does not cause cough.21Goldberg Al Dunlay MC Sweet CS Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension.Am J Cardiol. 1995; 75: 793-795Abstract Full Text PDF PubMed Scopus (284) Google Scholar An assumption is that it will decrease proteinuria; however, this has not yet been established. The creatinine and potassium levels should be measured after approximately 2 weeks and again after 6 to 8 weeks. Hyperkalemia, severe azotemia, and angioedema are contraindications to the use of an ACE inhibitor.9Williams GH Converting-enzyme inhibitors in the treatment of hypertension.N Engl J Med. 1988; 319: 1517-1525Crossref PubMed Google Scholar If an ACE inhibitor is given to a patient who has a slightly increased creatinine value, the creatinine concentration should be carefully monitored. Because such patients are susceptible to hyperkalemia, the potassium concentration should also be monitored frequently. Of the ACE inhibitors, most of the studies have been performed with captopril, but some studies have been done with longer-acting ACE inhibitors.10Overlack A Adamczak M Bachmann W Bonner G Bretzel RG Derichs R et al.ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases.Am J Med. 1994; 97: 126-134Abstract Full Text PDF PubMed Scopus (44) Google Scholar The longer action of the newer ACE inhibitors improves compliance. Because of the possibility of fetal or neonatal morbidity and possibly mortality, ACE inhibitors should not be given to pregnant women or to those planning a pregnancy.22Shotan A Widerhorn J Hurst A Elkayam U Risks of angiotensin-converting enzyme inhibition during pregnancy: experimental and clinical evidence, potential mechanisms, and recommendations for use.Am J Med. 1994; 96: 451-456Abstract Full Text PDF PubMed Scopus (218) Google ScholarTable 1Available Angiotensin-Converting Enzyme Inhibitors*When possible, diuretic doses should be decreased or discontinued before initiation of angiotensin-converting enzyme (ACE) inhibitors to prevent excessive hypotension. ACE inhibitors may cause hyperkalemia in patients with renal impairment or in those receiving potassium-sparing agents, and they can cause acute renal failure in patients with severe bilateral renal artery stenosis or severe stenosis of an artery supplying a solitary kidney.Data from the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure.2The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V).Arch Intern Med. 1993; 153: 154-183Crossref PubMed Scopus (2782) Google ScholarDrugUsual dosage range (total mg/day)Daily frequencyBenazepril10.0-40†Decrease dose in patients with serum creatinine levels that are >221 μπμ/L (2.5 mg/dL).Once or twiceCaptopril12.5-150†Decrease dose in patients with serum creatinine levels that are >221 μπμ/L (2.5 mg/dL).TwiceCilazapril2.5-5.0Once or twiceEnalapril2.5-40tOnce or twiceFosinopril10.0-40Once or twiceLisinopril5.0-40tOnce or twicePerindopril1.0-16fOnce or twiceQuinapril5.0-80tOnce or twiceRamipril1.25-20tOnce or twiceSpirapril12.5-50Once or twice* When possible, diuretic doses should be decreased or discontinued before initiation of angiotensin-converting enzyme (ACE) inhibitors to prevent excessive hypotension. ACE inhibitors may cause hyperkalemia in patients with renal impairment or in those receiving potassium-sparing agents, and they can cause acute renal failure in patients with severe bilateral renal artery stenosis or severe stenosis of an artery supplying a solitary kidney.† Decrease dose in patients with serum creatinine levels that are >221 μπμ/L (2.5 mg/dL). Open table in a new tab Calcium channel blockers may be of value in the treatment of hypertension in patients with diabetes, especially when advanced renal failure limits the use of an ACE inhibitor, when renal artery stenosis may be present, in elderly persons, and during pregnancy.14Ferrier C Ferrari P Weidmann P Keller U Beretta-Piccoli C Riesen WF Antihypertensive therapy with Ca2+: antagonist verapamil and/or ACE inhibitor enalapril in NIDDM patients.Diabetes Care. 1991; 14: 911-914Crossref PubMed Scopus (38) Google Scholar, 15Caldwell BV Treating hypertension in the diabetic patient: therapeutic goals and the role of calcium channel blockers.Clin Ther. 1993; 15: 618-636PubMed Google Scholar, 16ter Wee PM De Micheli AG Epstein M Effects of calcium antagonists on renal hemodynamics and progression of nondiabetic chronic renal disease.Arch Intern Med. 1994; 154: 1185-1202Crossref PubMed Google Scholar Long-acting preparations are preferable. The blood pressure level should be measured frequently (for example, several times a week), and doses should be slowly increased until adequate blood pressure control is achieved. The patient should be asked about constipation and peripheral edema. The presence of heart block is a contraindication to the use of calcium channel blockers. Concomitant use of β-adrenergic blockers and calcium channel blockers should be avoided if possible. Patients with congestive heart failure and a low ejection fraction will likely benefit from the use of ACE inhibitors, whereas calcium channel blockers may be preferable in patients with coronary artery disease. Data from a retrospective case-control study by investigators at the University of Washington suggested that patients with hypertension who are taking short-acting calcium channel blockers have a 60% higher chance of myocardial infarction than do patients receiving diuretics or β-blockers.23Psaty BM Heckbert SR Koepsell TD Siscovik DS Raghunathan TE Weiss NS et al.The risk of myocardial infarction associated with antihypertensive drug therapies.JAMA. 1995; 274: 620-625Crossref PubMed Scopus (971) Google Scholar An accompanying editorial raised the possibility that subtle differences in baseline risk factors could have affected the choice of medications and might have resulted in the observed increased risk of myocardial infarction in the group that received calcium channel blockers.24Buring JE Glynn RJ Hennekens CH Calcium channel blockers and myocardial infarction: a hypothesis formulated but not yet tested [edtiorial].JAMA. 1995; 274: 654-655Crossref PubMed Scopus (91) Google Scholar Obviously, more studies are needed. A large-scale multicenter prospective study sponsored by the National Institutes of Health is currently under way; however, results will not be available until the year 2000.25Lenfant C The calcium channel blocker scare: lessons for the future.Circulation. 1995; 91: 2855-2856Crossref PubMed Scopus (32) Google Scholar Thus, until data are available, it is probably appropriate to continue to use long-acting calcium channel blockers cautiously in patients whose blood pressure levels cannot be adequately controlled with other agents. Of the dihydropyridine calcium channel blockers, information about the effect of nifedipine on microalbuminuria is controversial.26Mimran A Insua A Ribstein J Monnier L Bringer J Mirouze J Contrasting effects of captopril and nifedipine in normotensive patients with insipient diabetic nephropathy.J Hypertens. 1988; 6: 919-923Crossref PubMed Scopus (90) Google Scholar, 27Melbourne Diabetic Nephropathy Study Group Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria.BMJ. 1991; 302: 210-216Crossref PubMed Google Scholar Other calcium channel blockers such as verapamil hydrochloride and diltiazem hydrochloride have been shown to decrease microalbuminuria; therefore, they may be preferable to nifedipine. In a recent study of nondiabetic persons that compared.4Nosadini R Fioretto P Trevisan R Crepaldi G Insulin-dependent diabetes mellitus and hypertension.Diabetes Care. 1991; 14: 210-219Crossref PubMed Scopus (28) Google Scholar six antihypertensive agents, results were favorable for diltiazem;28Materson BJ Reda DJ Cushman WC Massie BM Fries ED Kochar MS et al.Single-drug therapy for hypertension in men: a comparison of six antihypertensive agents with placebo.N Engl J Med. 1993; 328: 914-921Crossref PubMed Scopus (1196) Google Scholar however, superiority of one long-acting calcium channel blocker over the others was not established. The synergistic effect of calcium channel blockers and ACE inhibitors on microalbuminuria and for the prevention of progression of renal disease needs further studies. Evidence for improvement of insulin sensitivity by ACE inhibitors29Paolisso G Gambardella A Verza M D'Amore A Sgambato S Varricchio M ACE inhibition improves insulin-sensitivity in aged insulin-resistant hypertensive patients.J Hum Hypertens. 1992; 6: 175-179PubMed Google Scholar, 30Shionoiri H Ueda S Gotoh E Ito T Ogihara T Glucose and lipid metabolism during long-term lisinopril therapy in hypertensive patients.J Cardiovasc Pharmacol. 1990; 16: 905-909Crossref PubMed Scopus (20) Google Scholar and calcium channel blockers31Chellingsworth MC Kendall MJ Wright AD Singh BM Pasi J The effects of verapamil, diltiazem, nifedipine and propranolol on metabolic control in hypertensives with non-insulin dependent diabetes mellitus.J Hum Hypertens. 1989; 3: 35-39PubMed Google Scholar, 32Janka H-U Mehnert H Isradipinea dihydropyridine calcium antagonist with a favorable metabolic profile in hypertensive type II diabetics compared to nifedipine [abstract].J Cardiovasc Pharmacol. 1988; 12: S213Google Scholar also needs to be substantiated by more studies. Although controversy exists about the optimal level of blood pressure control, we believe that, in the absence of other contraindications, a reasonable blood pressure goal for a patient with type I diabetes and an increased microalbumin secretion would be 120/80 mm Hg or lower. Similarly, in the absence of other contraindications, a reasonable goal for a patient with type II diabetes or for a patient with type I diabetes with no increased microalbumin secretion would be a blood pressure of 130/85 mm Hg or lower.2The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V).Arch Intern Med. 1993; 153: 154-183Crossref PubMed Scopus (2782) Google Scholar, 14Ferrier C Ferrari P Weidmann P Keller U Beretta-Piccoli C Riesen WF Antihypertensive therapy with Ca2+: antagonist verapamil and/or ACE inhibitor enalapril in NIDDM patients.Diabetes Care. 1991; 14: 911-914Crossref PubMed Scopus (38) Google Scholar Care must be taken to ensure that the risk of therapy does not exceed potential benefits. If the previously mentioned blood pressure goals are not achieved and hypertension persists despite a moderate to maximal dose of an ACE inhibitor, other drugs should be added to the regimen, including low-dose hydrochlorothiazide, 12.5 to 25 mg; indapamide, 1.25 to 2.5 mg; or furosemide, 20 to 80 mg. Concerns about high mortality rates associated with diuretic therapy for patients with diabetes mellitus have been raised;33Siscovick DS Raghunathan TE Psaty BM Koepsell TD Wicklund KG Lin X et al.Diuretic therapy for hypertension and the risk of primary cardiac arrest.N Engl J Med. 1994; 330: 1852-1857Crossref PubMed Scopus (417) Google Scholar, 34Warram JH Laffel LMB Valsania P Christlieb AR Krolewski AS Excess mortality associated with diuretic therapy in diabetes mellitus.Arch Intern Med. 1991; 151: 1350-1356Crossref PubMed Scopus (142) Google Scholar however, lower doses maybe safe, and the addition of potassium-sparing drugs may decrease the risk of cardiac arrest.” For isolated systolic hypertension, low-dose diuretic therapy may be considered a suitable alternative to calcium channel blockers.35SHEP Cooperative Research Group Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP).JAMA. 1991; 265: 3255-3264Crossref PubMed Scopus (4626) Google Scholar If the first choice is a calcium channel blocker and edema is a problem, the addition of a diuretic may be the next step. When the serum creatinine concentration is greater than 2 mg/dL, a loop diuretic such as furosemide will likely be needed. If hypertension persists despite the combination of a diuretic, ACE inhibitor, and calcium channel blocker, an α-adrenergic blocking agent such as doxazosin mesylate, prazocin hydrochloride, or terazosin hydrochloride may be a helpful addition. A beneficial effect on insulin sensitivity and lipid profiles with such α-adrenergic blockers has been suggested.36Huapponen R Lehtonen A Vahatalo M Effect of doxazosin on insulin sensitivity in hypertensive non-insulin dependent diabetic patients.Eur J Clin Pharmacol. 1992; 43: 365-368Crossref PubMed Scopus (46) Google Scholar, 37Feher MD Doxazosin therapy in the treatment of diabetic hypertension.Am Heart J. 1991; 121: 1294-1301Abstract Full Text PDF PubMed Scopus (21) Google Scholar These drugs should be added cautiously (not to be used in the presence of severe autonomic neuropathy) because they may result in a pronounced decrease in blood pressure levels and cause syncope and dizziness, especially in elderly persons. Treatment of hypertension in patients with diabetes necessitates special considerations. Therapeutic goals and choice of medications differ from those for patients with hypertension who do not have diabetes. Various factors such as complications of diabetes, associated conditions, and cost of medications should be considered in the management of hypertension in patients with diabetes.